title: Cross-linking CD21/CD35 or CD19 increases both B7-1 and B7-2 expression on murine splenic B cells.
abstract: Activation of the complement cascade and ligation of complement C3 receptors on B cells represent an important bridge between innate and Ag-specific acquired immunity. We show here that cross-linking of mouse CD21 (complement receptor type 2, CR2, C3d receptor) and CD35 (complement receptor type 1, CR1, C3b/C4b receptor) or co-cross-linking of CD21/CD35 and surface IgM rapidly up-regulates both B7-1 and B7-2 expression on murine resting splenic B cells. CD21/CD35-mediated up-regulation of both B7-1 and B7-2 expression is observed within 14 h, while other stimuli up-regulate only B7-2 but not B7-1 at this early time point. Consistent with the increase in B7 levels, BALB/c B cells on which surface IgM and CD21/CD35 have been co-cross-linked stimulate C57BL/6 T cells more effectively than controls. This CD21/CD35-enhanced allogeneic MLR is blocked nearly completely by anti-B7-2 mAbs and partially by anti-B7-1 mAbs. In addition, cross-linking of CD19, which is physically associated with CD21/CD35, leads to increased B7-1 and B7-2 expression. These data suggest that CD21/CD35 ligation results in enhanced B cell Ag presentation using costimulatory mechanisms shared with other activators and thus works cooperatively in this process. Rapid up-regulation of B7-1 expression, a unique response to CD21/CD35 and CD19 cross-linking, may be a particularly important effect of C3-containing ligands. We propose that CD21/CD35- and CD19-mediated B7-1 and B7-2 up-regulation is an important mechanism by which complement activation links innate and acquired immunity.
authors.affiliation: Research Institute for Biological Science, Science University of Tokyo, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kozono
authors.forename: R
authors.initials: R
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Kozono
authors.forename: R G
authors.initials: RG
authors.lastname: Kelly
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis* / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D051940:B7-2 Antigen; D002460:Cell Line; D002478:Cells, Cultured; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017463:Receptors, Complement 3b / Q000276:immunology / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d